Research Progress of Traditional Chinese Medicine Intervention in Nrf2/HO-1 Signaling Pathway for Acute Pancreatitis： A Review / 中国实验方剂学杂志

Acute pancreatitis （AP） is a common clinical acute abdominal disease， which is characterized by acute onset， rapid development， severe disease， many complications， and high mortality rate. It can progress to severe AP （SAP） if not treated promptly in the early stage. The pathogenesis of AP is complex and involves multiple cellular and molecular levels. It is now clear that oxidative stress and reactive oxygen species （ROS） production are involved in the physiopathological process of AP， which is associated with a low quantity and activity of antioxidant enzymes in pancreatic cells. Nuclear factor E2-related factor 2 （Nrf2） serves as the ''golden key'' to maintain redox homeostasis in tissue cells and constitutes an important signaling pathway for antioxidant response and inflammation in vivo by collaborating with downstream antioxidant enzymes such as heme oxygenase-1 （HO-1）. Traditional Chinese medicine has unique efficacy in treating diseases due to its multi-component， multi-target， multi-drug delivery， and multi-formulation characteristics. Based on the concept of synergy between traditional Chinese and Western medicine， traditional Chinese medicine is becoming a new craze in the treatment of AP. The level of oxidative stress and Nrf2/HO-1 signaling pathway in AP pancreatic tissue are in a dynamic change process， and the intervention of traditional Chinese medicine can clean ROS production， affect the inflammatory pathway， and reduce oxidative stress damage， so as to protect against pancreatic injury. This suggests that this pathway plays an important role in AP. This article reviews the recent literature on the regulation of the Nrf2/HO-1 signaling pathway by traditional Chinese medicine for AP and summarizes that the monomers of traditional Chinese medicine targeting this pathway are mainly heat-clearing and detoxifying， blood-activating and blood-stasis-removing， and Qi benefiting and middle warming， and the compounds of traditional Chinese medicine include Yinchenhao Decoction and QingYi Ⅱ， so as to provide a new direction for the prevention and treatment of AP and further drug development.

Thrombosis of the Superior Mesenteric Artery and Hepatic Artery Secondary to Acute Necrotizing Pancreatitis: Case Report and Literature Review

We describe the case of a female patient with severe acute pancreatitis of biliary origin who presented with clinical deterioration. A thrombosis of the superior mesenteric artery and hepatic artery was identified as the cause, thus creating a rare vascular complication. She was taken for pharmacological and mechanical thrombectomy, with the subsequent death of the patient. Arterial vascular complications are an entity little recognized in the medical literature; they have a high mortality rate and pose a significant diagnostic and therapeutic challenge.

Se describe el caso de una paciente femenina con pancreatitis aguda grave de origen biliar quien presentó deterioro clínico, y como causa se identificó una trombosis de arteria mesentérica superior y arteria hepática, de modo que se configuró una complicación vascular poco frecuente. Fue llevada a trombectomía farmacológica y mecánica, con el posterior deceso de la paciente. Las complicaciones vasculares arteriales son una entidad poco reconocida en la literatura médica, tienen una alta tasa de mortalidad y suponen un reto diagnóstico y terapéutico importante.

Desbridamiento retroperitoneal video asistido: una nueva técnica quirúrgica para una vieja patología, la pancreatitis aguda severa presentación de caso clínico / Video-assisted retroperitoneal debridement: a new surgical technique for an old pathology, severe acute pancreatitis clinical case presentation

INTRODUCCIÓN: el desbridamiento retroperitoneal video asistido (DRVA) es una técnica mínimamente invasiva usada para el tratamiento de la necrosis pancreática infectada (NPI). MATERIAL Y MÉTODO: reporte de caso. RESULTADOS: se presenta un caso de pancreatitis aguda severa tratada con DRVA en una paciente femenina de 43 años, con un cuadro clínico de 5 días de evolución caracterizado por dolor abdominal espasmódico en hipocondrio derecho, de moderada intensidad, irradiado a epigastrio y en cinturón a ambos flancos. La paciente recibió atención privada en dos centros previos al ingreso al nuestro. Al ingreso, en el laboratorio, presenta leucocitosis y desvió izquierdo, amilasémia y lipasémia altas. Se realizaron tomografías contrastadas y punciones guiadas por TAC y DRVA cuando se evidencia necrosis amurallada. Se describe la técnica quirúrgica. Súbitamente la paciente presenta insuficiencia respiratoria y datos compatibles con tromboembolia pulmonar y fallece. CONCLUSIÓN: bajo la visión de terapia escalonada, el desbridamiento retroperitoneal video asistido va ganando adeptos en el manejo de la Pancreatitis Aguda Severa

BACKGROUND: video-assisted retroperitoneal debridement (VARD) is a minimally invasive technique used for the treatment of infected necrotizing pancreatitis. MATERIAL AND METHODS: case report. RESULTS: a case of severe necrotizing pancreatitis is presented in a 43 years old female patient, with 5 days clinical evolution with spasmodic abdominal pain in epigastrium and right hypochondrium of moderate intensity, irradiated to both flanks in belt. The patient received private care in two centers upon the admission in our hospital. In the laboratory at the admission, she showed leukocytosis and left deviation, high level in amylase and lipase. Contrasted enhanced tomography and guided punctures were realized and VARD were considered when evidence of wall of necrosis was observed in scanner. The surgical technique is described. Suddenly the patient presented acute respiratory failure with massive pulmonary thromboembolism and died. CONCLUSION: under the step-up approach vision, the video-assisted retroperitoneal debridement is gaining popularity in the management of the acute necrotizing pancreatitis

Función antiinflamatoria y antioxidante del ácido ursólico en la pancreatitis aguda inducida por ceruleína en ratas / Anti-inflammatory and anti-oxidant role of ursolic acid in cerulein-induced acute pancreatitis in rats

Resumen Antecedentes: El ácido ursólico se encuentra en numerosas plantas y se ha informado que tiene efectos antiproteasas, antioxidantes, antiinflamatorios, antimicrobianos, nefroprotectores, hepatoprotectores y cardioprotectores. Objetivo: Este estudio tuvo como objetivo investigar los efectos del ácido ursólico en la pancreatitis aguda inducida por ceruleína. Material y métodos: Treinta y dos ratas albinas Wistar fueron asignadas aleatoriamente a cuatro grupos iguales: grupo simulado, grupo de pancreatitis aguda, grupo de tratamiento y grupo de ácido ursólico. Resultados: Los niveles de amilasa sérica en los grupos de pancreatitis aguda y de tratamiento fueron significativamente más altos que en los otros grupos (p < 0.05). Además, los niveles séricos de IL-1β, IL-6 y TNF-α fueron significativamente más altos en el grupo de pancreatitis aguda en comparación con el grupo de tratamiento. Aunque la actividad oxidante total del tejido pancreático en ambos grupos fue similar, la capacidad antioxidante total del tejido pancreático en el grupo de tratamiento fue significativamente mayor. Conclusión: Se observó que el ácido ursólico reduce el daño al páncreas y órganos remotos en la pancreatitis aguda, al igual que el estrés oxidativo.

Abstract Background: Ursolic acid (UA) is found in many plants, and has been reported to have anti-protease, antioxidant, anti-inflammatory, antimicrobial, nephroprotective, hepatoprotective, and cardioprotective effects. Objective: The purpose of this study was to investigate the effects of ursolic acid in cerulein-induced acute pancreatitis (AP). Materials and methods: Thirty-two Wistar albino rats were randomly assigned to 4 equal groups: Sham, acute pancreatitis, treatment, and ursolic acid group. Results: Serum amylase levels in the AP and treatment groups were significantly higher than in the others (p < 0.05). In addition, serum IL-1β, IL-6, and TNF-α levels were significantly higher in the AP group in comparison with the treatment group. Although pancreatic tissue total oxidant activity in the AP and treatment groups was similar, pancreatic tissue total antioxidant capacity was significantly higher in the treatment group than in the AP group. Conclusions: Damage to the pancreas and remote organs in AP was observed to be reduced by UA. In addition, oxidative stress was observed to be decreased by the effect of UA.

Pancreatitis aguda asociada a balón intragástrico: reporte de caso y revisión de la literatura

La obesidad es una patología de importancia a nivel mundial porque conlleva a una alta carga de mortalidad y morbilidad. El balón intragástrico representa una técnica no quirúrgica empleada cada vez con más frecuencia para lograr pérdida de peso. Si bien, este se considera un método seguro, se han reportado algunas complicaciones desde náuseas y vómitos, hasta eventos adversos graves, tales como perforación. La pancreatitis aguda constituye una complicación muy rara del balón intragástrico y se atribuye su efecto a la compresión directa que ejerce sobre el páncreas. Presentamos el caso de una paciente mujer de 21 años, quien después de 7 meses de colocación de balón intragástrico, cursó con dolor abdominal, náuseas y vómitos, asociados a elevación de enzimas pancreáticas. Se hizo diagnóstico de pancreatitis aguda y se corroboró compresión de la cola del páncreas mediante estudio tomográfico. Se decidió retiro del balón mediante endoscopía, cursando luego con evolución favorable.

Obesity is a pathology of importance worldwide because it leads to a high burden of mortality and morbidity. The intragastric balloon represents a non-surgical technique used more and more frequently to achieve weight loss. Although this is considered a safe method, some complications have been reported, from nausea and vomiting to serious adverse events, such as perforation. Acute pancreatitis is a very rare complication of the intragastric balloon, and its effect is attributed to the direct compression it exerts on the pancreas. We present the case of a 21-year-old female patient who, after 7 months of intragastric balloon placement, developed abdominal pain, nausea, and vomiting, associated with elevated pancreatic enzymes. A diagnosis of acute pancreatitis was made and compression of the tail of the pancreas was confirmed by tomographic study. It was decided to remove the balloon by endoscopy, which then progressed favorably.

Effects of somatostatin in combination with early hemoperfusion on inflammatory, hemorheological and oxidative parameters during the treatment of acute pancreatitis / Efectos de la somatostatina en combinación con hemoperfusión precoz sobre parámetros inflamatorios, hemorreológicos y oxidativos durante el tratamiento de la pancreatitis aguda

Abstract We aimed to evaluate the effects of somatostatin combined with early hemoperfusion on inflammatory and stress responses during acute pancreatitis (AP) treatment. A total of 159 AP patients treated from September 2016 to January 2020 were randomly divided into three groups A-C (n=53). In addition to routine treatment, groups A-C were additionally given somatostatin, early hemoperfusion, and somatostatin combined with early hemoperfusion, respectively. Their inflammatory factors, stress response, intestinal mucosal barrier, hemorheological indices, recovery time, length of stay, clinical efficacy, and adverse reactions were compared. The levels of serum interleukin-10 (IL - 10), catalase and glutathione peroxidase rose in the three groups after ten days of treatment, compared with values before treatment, being the highest rise in group C. The levels of IL -18, tumor necrosis factor-α, soluble intercellular adhesion molecule-1, procalcitonin, high mobility group protein B1, lipid hydrogen peroxide, advanced oxidation protein products, epinephrine, cortisol, D-lactic acid, diamine oxidase, and endotoxin decreased after ten days of treatment compared with those before treatment, which were lowest in group C (P<0.05). After ten days of treatment, the levels of hemorheological indices were significantly lower than those before treatment (P<0.05). Compared with groups A and B, group C had a shorter recovery time of urine amylase, bowel sound and passing gas, remission time of abdominal pain, length of stay, and a higher total response rate (P<0.05). During AP treatment, somatostatin combined with early hemoperfusion effectively relieved inflammatory and stress responses, protected the intestinal mucosal barrier function and improved the hemorheology, thereby promoting the recovery and benefiting the prognosis of patients.

Resumen Nuestro objetivo fue evaluar los efectos de la somatostatina combinada con hemoperfusión temprana sobre las respuestas inflamatorias y de estrés durante el tratamiento de la pancreatitis aguda (PA). Un total de 159 pacientes con PA tratados entre septiembre de 2016 y enero de 2020 se dividieron aleatoriamente en tres grupos A-C (n=53). Con base en el tratamiento de rutina, los grupos A-C recibieron además somatostatina, hemoperfusión temprana y somatostatina combinada con hemoperfusión temprana, respectivamente. Se compararon sus factores inflamatorios, respuesta al estrés, barrera de la mucosa intestinal, índices hemorreológicos, tiempo de recuperación, tiempo de estancia, eficacia clínica y reacciones adversas. Los niveles séricos de interleucina-10 (IL -10), catalasa y glutatión peroxidasa aumentaron en los tres grupos después de 10 días de tratamiento, comparados con los valores antes del tratamiento, siendo más elevados en el grupo C. Los niveles de IL - 18, factor de necrosis tumoral α, molécula de adhesión intercelular 1 soluble, procalcitonina, proteína B1 del grupo de alta movilidad, peróxido de hidrógeno lipídico, los productos proteicos de oxidación avanzada, epinefrina, cortisol, ácido D-láctico, diaminooxidasa y endotoxina disminuyeron después de 10 días de tratamiento en comparación con los previos al tratamiento, que fueron más bajos en el grupo C (P<0,05). Después de 10 días de tratamiento, los índices hemorreológicos fueron significativamente menores que los previos al tratamiento (P<0,05). En comparación con los grupos A y B, el grupo C tuvo un tiempo de recuperación más corto de amilasa en orina, sonido y escape intestinal, tiempo de remisión del dolor abdominal y tiempo de estancia, y una tasa de respuesta total más alta (P<0,05). Durante el tratamiento de la AP, la somatostatina combinada con hemoperfusión precoz alivia eficazmente las respuestas inflamatorias y de estrés, protege la función de la barrera de la mucosa intestinal y mejora la hemorología, favoreciendo la recuperación y beneficiando el pronóstico de los pacientes.

Pancreatitis aguda: Puntos clave. Revisión argumentativa de la literatura / Acute pancreatitis: Key points. Argumentative review of the literature

Introducción. La pancreatitis aguda es una condición gastrointestinal común que se asocia a una importante morbimortalidad. Se estima que su incidencia es de 34 por cada 100.000 habitantes, afecta principalmente a adultos a partir de la sexta década de la vida y en nuestra región es debida en la mayoría de los casos a cálculos biliares. Métodos. Se hizo una revisión de los aspectos fundamentales de esta patología, común y potencialmente mortal. Resultados. El diagnóstico requiere del hallazgo de manifestaciones clínicas, aumento de las enzimas pancreáticas en suero y, en ocasiones, el uso de imágenes diagnósticas. Se puede clasificar en leve, moderada y severa, lo cual es fundamental para determinar la necesidad de tratamiento y vigilancia en una unidad de cuidados intensivos. Conclusión. En la actualidad los pilares de manejo de la pancreatitis aguda son la terapia temprana con líquidos, tratamiento del dolor, inicio precoz de la vía oral y resolución del factor etiológico desencadenante. En presencia de complicaciones o un curso severo de enfermedad, pueden requerirse manejo antibiótico e intervenciones invasivas

Introduction. Acute pancreatitis is a common gastrointestinal condition that is associated with significant morbidity and mortality. It is estimated that its incidence is 34 per 100,000 inhabitants, it mainly affects adults from the sixth decade of life, and in our region, most of the cases are secondary to gallbladder stones. Methods. We present a review of the fundamental aspects of this disease, common and potentially fatal. Results. Diagnosis requires finding clinical manifestations, increased serum pancreatic enzymes, and sometimes the use of diagnostic imaging. It can be classified as mild, moderate and severe, which is essential to determine the need for treatment and monitoring in an intensive care unit. Conclusion. Currently, the pillars of management of acute pancreatitis are early fluid therapy, pain management, early oral food intake, and resolution of the etiology. In the presence of complications or a severe course of the disease, antibiotic management and invasive interventions may be required

EVALUATION AND PROGNOSTIC CORRELATION OF ACUTE PANCREATITIS USING CT SEVERITY INDEX

Background: Of all abdominal emergencies, pancreatitis is one of the most complicated and clinically dif?cult. The preferred imaging technique for determining the severity of acute pancreatitis and its consequences is computed tomography (CT). To evaluate the clinical outcome of acute pancreatitis and prognostic Aim: correlation based on the CT severity index. We included 30 patients with suspected acute pancreatitis Settings and Design: attending department of Radio Diagnosis, KVG medical college and hospital during the study period (January 2022 to May 2022). All the patients were evaluated by contrast enhanced CT. The severity of pancreatitis was scored using CT severity index (Balthazar), modi?ed severity index (Mortele) and revised Atlanta classi?cation and the cases were classi?ed into mild, moderate and severe. The outcome parameters studied were Length of hospital stay, Need for surgery or percutaneous intervention, incidence of infection or organ failure and death. The age group of patients was 16 to 69 years with Results: maximum patients (36%) between 25 and 35 years. Majority were males (81%). According to Modi?ed CT Severity Index, 15% patients had mild, 42% patients had moderate and 43% had severe pancreatitis. Majority of the cases (44%) were categorized as severe pancreatitis according modi?ed Mortele CT score. Majority of the cases were categorized as mild pancreatitis according Balthazar CTSI score and revised Atlanta classi?cation. 38% patients are considered to have end organ failure. Hepatic failure is the most common system failure seen in 22% patients. 36% patients had evidence of systemic infection. 10% patients required surgical interventions. The score is simpler to calculate and the inter-observer variability is Conclusions: decreased using the modi?ed CT severity index.

Pancreatitis aguda por hipertrigliceridemia severa, caracterización en un hospital terciario / Acute pancreatitis due to severe hypertriglyceridemia, characterization in a tertiary hospital

La hipertrigliceridemia severa es una de las principales causas etiológicas de la pancreatitis aguda, donde la literatura internacional la posiciona como la tercera causa. Sus causas gatillantes, comorbilidades, severidad y evolución son importantes de conocer para evitar futuros episodios. En Chile, a nuestro entender, no tenemos literatura sobre esta asociación, por lo que presentamos datos de un hospital terciario, destacando 15 casos de pancreatitis aguda en 5 años de estudio, casi la mitad de ellos con antecedentes previos de hipertrigliceridemia, un porcentaje importante de los casos con cuadros graves y con complicaciones intrahospitalarias y que la diabetes mellitus tipo 2 fue la principal condición asociada a la hipertrigliceridemia severa.

Severe hypertriglyceridaemia is one of the main aetiological causes of acute pancreatitis, with international literature ranking it as the third leading cause. Its triggering causes, comorbidities, severity and evolution are important to know in order to avoid future episodes. In Chile, to our knowledge, we have no literature on this association, so we present data from a tertiary hospital, highlighting 15 cases of acute pancreatitis in 5 years of study, almost half of them with a previous history of hypertriglyceridaemia, a significant percentage of cases with severe symptoms and in-hospital complications, and that type 2 diabetes mellitus was the main condition associated with severe hypertriglyceridaemia.

Combined superior mesenteric artery syndrome and nutcraker syndrome presenting as acute pancreatitis: a case report / Síndrome da artéria mesentérica superior em combinação com síndrome de quebra-nozes manifestando-se como pancreatite aguda: relato de caso

Abstract Superior mesenteric artery syndrome designates compression of the third part of the duodenum between the superior mesenteric artery and the aorta. This condition has a low incidence, being more common in thin young women. Nutcracker syndrome is compression of the left renal vein between the superior mesenteric artery and the aorta. Both entities are rare, and their coexistence has been reported in a few cases. Conservative treatment targeting weight gain is sufficient in most cases. An association between the superior mesenteric artery syndrome and acute pancreatitis has rarely been reported. We intend to describe the case of an 18-year-old girl who was admitted to the emergency room with epigastric pain and emesis. Our investigation revealed acute acalculous pancreatitis. During work-up, we discovered superior mesenteric artery syndrome and a compressed left renal vein. The patient is on conservative treatment, and her symptoms have improved.

Resumo A síndrome da artéria mesentérica superior designa compressão da terceira parte do duodeno pela artéria mesentérica superior e a aorta. Essa condição tem uma baixa incidência, sendo mais comum em mulheres jovens magras. A síndrome de quebra-nozes resulta da compressão da veia renal esquerda pela artéria mesentérica superior e a aorta. Ambas as entidades são raras, e a sua coexistência foi descrita em poucos casos. Tratamento conservador com o objetivo de ganho ponderal é suficiente na maioria dos casos. A associação entre a síndrome da artéria mesentérica superior e a pancreatite aguda foi raramente relatada. Pretendemos descrever o caso de uma jovem de 18 anos que recorreu ao serviço de urgência com epigastralgia e vômitos. A investigação realizada revelou pancreatite aguda alitiásica. Durante o estudo complementar, foi identificada a síndrome da artéria mesentérica superior, bem como uma veia renal esquerda comprimida. A paciente encontra-se em tratamento conservador, apresentando melhora clínica.

Gelsolin inhibits autophagy by regulating actin depolymerization in pancreatic ductal epithelial cells in acute pancreatitis

Gelsolin (GSN) can sever actin filaments associated with autophagy. This study investigated how GSN-regulated actin filaments control autophagy in pancreatic ductal epithelial cells (PDECs) in acute pancreatitis (AP). AP was produced in a rat model and PDECs using caerulein (CAE). Rat pancreatic duct tissue and HPDE6-C7 cells were extracted at 6, 12, 24, and 48 h after CAE treatment. HPDE6-C7 cells in the presence of CAE were treated with cytochalasin B (CB) or silenced for GSN for 24 h. Pancreatic histopathology and serum amylase levels were analyzed. Cellular ultrastructure and autophagy in PDECs were observed by transmission electron microscopy after 24 h of CAE treatment. The expression of GSN and autophagy markers LC3, P62, and LAMP2 was evaluated in PDECs by immunohistochemistry and western blotting. Actin filaments were observed microscopically. Amylase levels were highest at 6 h of AP, and pancreatic tissue damage increased over time. Mitochondrial vacuolization and autophagy were observed in PDECs. CAE increased GSN expression in these cells over time, increased the LC3-II/LC3-I ratio and LAMP2 expression at 24 and 6 h of treatment, respectively, and decreased P62 expression at all time points. CB treatment for 24 h decreased the LC3-II/LC3-I ratio and LAMP2 expression, increased P62 levels, but had no impact on GSN expression in CAE-treated PDECs. CAE induced actin depolymerization, and CB potentiated this effect. GSN silencing increased the LC3-II/LC3-I ratio and LAMP2 expression and reduced actin depolymerization in CAE-treated PDECs. GSN may inhibit autophagosome biogenesis and autophagosome-lysosome fusion by increasing actin depolymerization in PDECs in AP.

Dahuang Mudantang Alleviates Intestinal Injury in Rat Model of Acute Pancreatitis by Regulating HMGB1/RAGE/NF-κB Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Dahuang Mudantang in alleviating the intestinal injury in the rat model of acute pancreatitis via the high-mobility group box 1 （HMGB1）/receptor for advanced glycation endproduct （RAGE）/nuclear factor-κB （NF-κB） signaling pathway. MethodOne hundred and twenty SPF-grade Wistar rats received retrograde injection of 5% sodium taurocholate into the biliopancreatic duct for the modeling of intestinal injury in acute pancreatitis. The rats were randomized into blank， model， low-， medium-， and high-dose （3.5， 7， 14 g·kg-1， administrated by gavage） Dahuang Mudantang， and octreotide （1×10-5 g·kg-1， subcutaneous injection） groups （n=20）. The rats in blank and model groups received equal volume of distilled water by gavage. Drugs were administered 1 h before and every 12 h after modeling， and samples were collected 24 h after modeling. The general status of the rats was observed. The biochemical methods were employed to measure the levels of amylase （AMS） and C-reactive protein （CRP） in the serum. The enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of tumor necrosis factor （TNF）-α， interleukin （IL）-1β， and IL-6 in the colon tissue. The morphological changes of pancreatic and colon tissues were observed by hematoxylin-eosin （HE） staining. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were employed to measure the expression levels of HMGB1， RAGE， inhibitor of NF-κB kinase （IKK）， and NF-κB suppressor protein α（IκBα）in the colon tissue. ResultThe rats in the model group showed poor general survival， writhing response， reduced frequency of defecation， and dry stool. The symptoms of rats in the model group were mitigated in each treatment group， and the high-dose Dahuang Mudantang showed the most significant effect. Compared with the normal group， the model group had elevated AMS and CRP levels （P<0.05）， which were lowered by Dahuang Mudantang （P<0.05）， especially that at the high dose （P<0.05）. Compared with the normal group， the modeling elevated that levels of TNF-α， IL-1β， and IL-6 （P<0.05）. Such elevations were lowered by Dahuang Mudantang （P<0.05）， and the high-dose group and the octreotide group showed better performance （P<0.05）. The modeling caused necrotic， congested， and destructed pancreatic and colonic tissues， which were ameliorated by the drugs， especially high-dose Dahuang Mudantang. Compared with the normal group， the modeling up-regulated the mRNA levels of HMGB1， RAGE， IKK， IκBα， and NF-κB （P<0.05）. Compared with the model group， Dahuang Mudantang and octreotide down-regulated the mRNA levels of HMGB1， RAGE， IKK， IκBα， and NF-κB （P<0.05）， and the high-dose Dahuang Mudantang demonstrated the best performance （P<0.05）. Western blot results showed a trend consistent with the results of Real-time PCR. ConclusionDahuang Mudantang can improved the general status， reduce inflammation， and alleviate histopathological changes in the pancreatic and colon tissues in the rat model of acute pancreatitis by inhibiting the HMGB1/RAGE/NF-κB signaling pathway.

Establishment and evaluation of early in-hospital death prediction model for patients with acute pancreatitis in intensive care unit / 中华危重病急救医学

Objective:To investigate the death risk prediction factors of acute pancreatitis (AP) patients in intensive care unit (ICU), and to establish a death prediction model and evaluate its efficacy.Methods:A retrospective cohort study was conducted using the data in the Medical Information Mart for Intensive Care-Ⅲ (MIMIC-Ⅲ). The clinical data of 285 AP patients admitted to the ICU in the database were collected, including age, gender, blood routine and blood biochemical indicators, comorbidities, simplified acute physiology score Ⅲ (SAPS Ⅲ) and hospital prognosis. By using univariate analysis, the differences in the clinical data of the patients were compared between the two groups. Binary multivariate Logistic regression analysis was used to screen out independent predictors of in-hospital death in AP patients. A death prediction model was established, and the nomogram was drawn. The receiver operator characteristic curve (ROC curve) was plotted, and the area under the ROC curve (AUC) was used to test the discrimination of the prediction model. In addition, the prediction model was compared with the SAPSⅢ score in predicting in-hospital death. The calibration ability of the prediction model was evaluated by the Hosmer-Lemeshow goodness of fit test, and a calibration map was drawn to show the calibration degree of the prediction model.Results:Among 285 patients with AP, 29 patients died in the hospital and 256 patients survived. Univariate analysis showed that the patients in the death group were older than those in the survival group (years old: 70±17 vs. 58±16), and had higher white blood cell count (WBC), total bilirubin (TBil), serum creatinine (SCr), blood urea nitrogen (BUN), red blood cell volume distribution width (RDW), proportion of congestive heart failure and SAPSⅢ score [WBC (×10 9/L): 18.5 (13.9, 24.3) vs. 13.2 (9.3, 17.9), TBil (μmol/L): 29.1 (15.4, 66.7) vs. 16.2 (10.3, 29.1), SCr (μmol/L): 114.9 (88.4, 300.6) vs. 79.6 (53.0, 114.9), BUN (mmol/L): 13.9 (9.3, 17.8) vs. 6.1 (3.7, 9.6), RDW: 0.152 (0.141, 0.165) vs. 0.141 (0.134, 0.150), congestive heart failure: 34.5% vs. 14.8%, SAPSⅢ score: 66 (52, 90) vs. 39 (30, 48), all P < 0.05]. Multivariate Logistic regression analysis showed that age [odds ratio ( OR) = 1.038, 95% confidence interval (95% CI) was 1.005-1.073], WBC ( OR = 1.103, 95% CI was 1.038-1.172), TBil ( OR = 1.247, 95% CI was 1.066-1.459), BUN ( OR = 1.034, 95% CI was 1.014-1.055) and RDW ( OR = 1.344, 95% CI was 1.024-1.764) were independent risk predictors of in-hospital death in patients with AP. Logistic regression model was established: Logit ( P) = 0.037×age+0.098×WBC+0.221×TBil+0.033×BUN+0.296×RDW-12.133. ROC curve analysis showed that the AUC of the Logistic regression model for predicting the in-hospital death of patients with AP was 0.870 (95% CI was 0.794-0.946), the sensitivity was 86.2%, and the specificity was 78.5%, indicating that the model had good predictive performance, and it was superior to the SAPSⅢ score [AUC was 0.831 (95% CI was 0.754-0.907), the sensitivity was 82.8%, and the specificity was 75.4%]. A nomogram model was established based on the result of multivariate Logistic regression analysis. The calibration map showed that the calibration curve of the nomogram model was very close to the standard curve, with the goodness of fit test: χ 2 = 6.986, P = 0.538, indicating that the consistency between the predicted death risk of the nomogram model and the actual occurrence risk was relatively high. Conclusions:The older the AP patient is, the higher the WBC, TBil, BUN, and RDW, and the greater the risk of hospital death. The death prediction Logistic regression model and nomogram model constructed based on the above indicators have good discrimination ability and high accuracy for high-risk patients with hospital death, which can accurately predict the probability of death in AP patients and provide a basis for prognosis judgment and clinical treatment of AP patients.

Predictive value of diaphragm thickening fraction and intra-abdominal pressure monitoring-oriented risk prediction model for weaning failure in patients with severe acute pancreatitis / 中华危重病急救医学

Objective:To establish a risk prediction model dominated by diaphragm thickening fraction (DTF) and intra-abdominal pressure (IAP) monitoring, and to explore the predictive value of the model for weaning failure in patients with severe acute pancreatitis (SAP).Methods:A prospective research was conducted. Sixty-three patients undergoing invasive mechanical ventilation treatment who diagnosed with SAP admitted to intensive care unit of the First Affiliated Hospital of Jinzhou Medical University from August 2020 to October 2021 were enrolled. The spontaneous breathing trial (SBT) was carried out when the clinical weaning criteria was met. The stable cardiovascular status, good pulmonary function, no chest and abdominal contradictory movement, and adequate oxygenation were defined as successful weaning. Otherwise, it was defined as failure weaning. The clinical indicators such as SBT 30-minure DTF, IAP, tidal volume (VT), respiratory rate (RR), body mass index (BMI), and blood lactic acid (Lac) were compared between the weaning success group and the weaning failure group. The indicators with statistically significant differences in the single-factor analysis were included in the secondary multivariable Logistic regression analysis to establish a risk prediction model. The correlation between the DTF and IAP at 30 minutes of SBT was analyzed. Receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of the risk prediction model for SAP patient withdrawal failure at 30 minutes of SBT.Results:Finally, 63 patients with SAP were enrolled. Among the 63 patients, 42 were successfully weaned and 21 failed. There were no significant differences in age, gender, and oxygenation index (PaO 2/FiO 2), sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score at admission between the two groups, indicating that the data in the two groups were comparable. Compared with the weaning success group, IAP, RR, BMI and Lac at 30 minutes of SBT in the weaning failure group were significantly increased [IAP (mmHg, 1 mmHg≈0.133 kPa): 14.05±3.79 vs. 12.12±3.36, RR (times/min): 25.43±8.10 vs. 22.02±5.05, BMI (kg/m 2): 23.71±2.80 vs. 21.74±3.79, Lac (mmol/L): 5.27±1.69 vs. 4.55±1.09, all P < 0.05], while DTF and VT were significantly decreased [DTF: (29.76±3.45)% vs. (31.86±3.67)%, VT (mL): 379.00±98.74 vs. 413.60±33.68, both P < 0.05]. Secondary multivariable Logistic regression analysis showed that DTF [odds ratio ( OR) = 0.758, 95% confidence interval (95% CI) was 0.584-0.983, P = 0.037], IAP ( OR = 1.276, 95% CI was 1.025-1.582, P = 0.029), and RR ( OR = 1.145, 95% CI was 1.014-1.294, P = 0.029) were independent risk factors for SBT withdrawal failure in 30 minutes in SAP patients. The above risk factors were used to establish the risk prediction model of aircraft withdrawal failure at 30 minutes of SBT: Logit P = -0.237-0.277×DTF+0.242×IAP+0.136×RR. Pearson correlation analysis showed that SBT 30-minute DTF was significantly correlated with IAP in SAP patients, and showed a significant positive correlation ( r = 0.313, P = 0.012). The ROC curve analysis results showed that area under the ROC curve (AUC) of the risk prediction model for SAP patient withdrawal failure at 30 minutes of SBT was 0.716, 95% CI was 0.559-0.873, P = 0.003, with the sensitivity of 85.7% and the specificity of 78.6%. Conclusions:DTF, IAP and RR were independent risk factors for SBT withdrawal failure in 30 minutes in SAP patients. The DTF and IAP monitoring-oriented risk prediction model based on the above three variables has a good predictive value for weaning failure in patients with SAP.

Dachengqi decoction reduces inflammatory response and promotes recovery of gastrointestinal function in patients with mild acute pancreatitis by regulating the intestinal microbiota / 中华危重病急救医学

Objective:To explore the therapeutic effect and mechanism of Dachengqi decoction on patients with mild acute pancreatitis (MAP).Methods:A parallel randomized controlled trial was conducted. Sixty-eight patients with acute pancreatitis (AP) admitted to Shanghai Traditional Chinese Medicine (TCM)-Integrated Hospital from March 2018 to February 2021 were enrolled. Referring to the condition on admission of the patients and whether they agreed to receive the Dachengqi decoction or not, they were divided into conventional treatment group and Dachengqi decoction group according to the principle of 1∶1 equal randomness. Meanwhile, 20 healthy volunteers were recruited as controls. Both groups of patients were treated with octreotide, fasting, gastrointestinal decompression, antipyretic and analgesic, anti-inflammatory, inhibition of gastric acid and pancreatic juice secretion, maintenance of electrolyte balance and other western conventional medicine. The patients in the Dachengqi decoction group received Dachengqi decoction orally on the basis of routine treatment, 100 mL each time, twice a day, for seven consecutive days. The inflammation parameters [white blood cell count (WBC), C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6)] before and after treatment and the recovery time of gastrointestinal function (first exhaust time, time to recover bowel sounds, first defecation time) of patients were recorded. 16S rRNA gene sequencing of stool samples was recorded, and normalized data were obtained after quality control and other related processing. The data were subjected to diversity analysis (Alpha diversity and Beta diversity) and linear discriminant analysis effect size analysis (LEfSe analysis) to observe changes in the gut microbiota of MAP patients. Spearman rank correlation coefficient was used to analyze the correlation between inflammatory indexes and microorganisms at the intestinal genus level. Blood, urine, stool samples, renal function, and electrocardiogram (ECG) during treatment of MAP patients were detected to assess the safety of the treatment.Results:Of the 68 patients with AP, 16 were excluded from moderate-severe AP, 4 were not collected or voluntarily abandoned treatment. Finally, 48 patients with MAP were enrolled, 24 in the conventional treatment group and 24 in the Dachengqi decoction group. The inflammation parameters levels at 7 days of treatment in both groups were significantly lower than those before treatment. CRP, PCT and IL-6 levels in the Dachengqi decoction group were significantly lower than those in the conventional treatment group [CRP (mg/L): 8.50 (3.50, 13.00) vs. 16.00 (9.25, 29.75), PCT (μg/L): 0.06 (0.03, 0.08) vs. 0.09 (0.05, 0.11), IL-6 (ng/L): 6.36 (3.96, 10.79) vs. 13.24 (6.69, 18.87), all P < 0.05]. The first exhaust time, time to recover bowel sounds and first defecation time in the Dachengqi decoction group were significantly shorter than those in the conventional treatment group [first exhaust time (days): 1.62±0.65 vs. 2.80±0.65, time to recover bowel sounds (days): 1.13±0.58 vs. 2.31±0.76, first defecation time (days): 3.12±0.75 vs. 4.39±0.76, all P < 0.05]. The analysis of intestinal microflora diversity showed that both the diversity and abundance of microbial communities were the highest in the healthy control group and the lowest in the conventional treatment group. In addition, the coincidence degree of microbial communities in healthy controls and MAP patients was small, while the coincidence degree of MAP patients among different treatment methods was relatively large. LEfSe analysis showed that Dachengqi decoction reduced the relative abundance of Escherichia coli-Shigella and Clostridium erysipelae, and increased the relative abundance of three beneficial bacteria, namely Lactobacillus, Rombutzia and Brutella. In the intestines of MAP patients, Lactobacillus mucilaginus and Lactobacillus conjunctus were significantly enriched. Correlation analysis showed that positive correlations between Escherichia coli- Shigella and the four inflammatory indicators including WBC, CRP, PCT, IL-6 were statistically significant ( r value was 0.31, 0.41, 0.57, 0.43, respectively, all P < 0.05). There was no significant correlation between other bacteria and inflammatory indicators. During the treatment, there was no obvious abnormality in blood, urine and feces, renal function and ECG of MAP patients. Conclusions:Dachengqi decoction could reduce inflammatory responses and promote recovery of intestinal microecological balance and gastrointestinal function in patients with MAP by regulating the composition of intestinal flora. No significant adverse effects were observed during the treatment period.

Construction and evaluation of a prognostic model for severe acute pancreatitis based on CT scores and inflammatory factors / 中华危重病急救医学

Objective:To construct a prognostic model for severe acute pancreatitis (SAP) based on CT scores and inflammatory factors, and to evaluate its efficacy.Methods:128 patients with SAP diagnosed admitted to the First Hospital Affiliated to Hebei North College from March 2019 to December 2021 were enrolled and given Ulinastatin combined with continuous blood purification therapy. The levels of C-reactive protein (CRP), procalcitonin (PCT), interleukins (IL-6, IL-8), tumor necrosis factor-α (TNF-α), and D-dimer were measured before and on the third day of treatment. An abdominal CT was performed on the third day of treatment to assess the modified CT severity index (MCTSI) and extra-pancreatic inflammatory CT score (EPIC). Patients were divided into the survival group ( n = 94) and the death group ( n = 34) according to the 28-day survival prognosis after admission. The risk factors for the SAP prognosis were analyzed using Logistic regression, which was then used to build nomogram regression models. The value of the model was evaluated using the concordance index (C-index), calibration curves and decision curve analysis (DCA). Results:Before treatment, the levels of CRP, PCT, IL-6, IL-8 and D-dimer in the death group were higher than those in the survival group. After treatment, the levels of IL-6, IL-8 and TNF-α in the death group were higher than those in the survival group. MCTSI and EPIC scores in the survival group were lower than those in the death group. Logistic regression analysis shows that, pre-treatment CRP > 140.70 mg/L, D-dimer > 2.00 mg/L, and post-treatment IL-6 > 31.28 ng/L, IL-8 > 31.04 ng/L, TNF-α > 31.04 ng/L, and MCTSI > 8 points were all independent risk factors for SAP prognosis [odds ratios ( OR) and 95% confidence intervals (95% CI) were 8.939 (1.792-44.575), 6.369 (1.368-29.640), 8.546 (1.664-43.896), 5.239 (1.108-24.769), 4.808 (1.126-20.525), 18.569 (3.931-87.725), all P < 0.05]. Model 1 (consisting of pre-treatment CRP, D-dimer, and post-treatment IL-6, IL-8 and TNF-α) had a lower C-index than that model 2 (consisting of pre-treatment CRP, D-dimer, and post-treatment IL-6, IL-8 and TNF-α, and MCTSI; 0.988 vs. 0.995). The mean absolute error (MAE) and mean square error (MSE) of model 1 (0.034, 0.003) were higher than those of model 2 (0.017, 0.001). When the threshold probability was in the range of 0-0.66 or 0.72-1.00, the net benefit of model 1 was lower than that of model 2. When the threshold probability was in the range of 0.66-0.72, the net benefit of model 1 was higher than that of model 2. In addition, model 2 had a higher C-index than acute physiology and chronic health evaluationⅡ (APACHE Ⅱ) and bedside index of acute pancreatitis severity (BISAP, 0.995 vs. 0.833, 0.751). Model 2 had a lower MAE (0.017) and MSE (0.001) than APACHEⅡ (0.041, 0.002). Model 2 had a lower MAE than BISAP (0.025). Model 2 had a higher net benefit than both APACHEⅡ and BISAP. Conclusion:The prognostic assessment model of SAP consisting of pre-treatment CRP, D-dimer, and post-treatment IL-6, IL-8 and TNF-α, and MCTSI has high discrimination, precision and clinical application value, and is superior to APACHEⅡ and BISAP.

Progress on enteral nutrition therapy for acute pancreatitis / 中华临床营养杂志

Acute pancreatitis (AP) is an acute inflammatory disease of various severity, characterized by upper abdominal pain, elevated pancreatic enzymes, and changes in imaging features of the pancreas. According to the degree of pancreatic injury and the presence and duration of systemic organ failure, AP is classified into mild, moderate, or severe disease. Most AP patients experience mild disease and recover quickly, while up to 20% progress to moderate or severe disease, with an estimated risk of death as high as 30%. Severe acute pancreatitis (SAP) is a clinical emergency with a critical condition and poor prognosis, especially in patients with pancreatic and/or peripancreatic tissue infection and necrosis. AP is essentially an inflammatory process that can lead to protein catabolism and increased metabolic rates, further resulting in negative nitrogen balance. The goal of nutritional support therapy for AP is to correct negative nitrogen balance, reduce inflammation, and improve prognosis. Enteral nutrition therapy is an important component of clinical treatment of SAP. This review aims to summarize the nutritional support treatment in AP based on the existing clinical data and experience.

Clinical features and risk factors of recurrent acute pancreatitis / 中华胰腺病杂志

Objective:To explore the clinical characteristics and to analyze the risk factors of recurrent acute pancreatitis (RAP).Methods:The clinical data of 3 022 patients with AP from AP database of the Affiliated Hospital of Southwest Medical University between January 2013 and December 2019 were retrospectively analyzed. According to with or without AP relapse and RAP diagnostic criteria, the patients were divided into initial group ( n=2 187) and recurrent group ( n=835). General characteristics, clinical data, and prognostic indicators were compared between the two groups. Multivariate logistic regression analysis was used to explore the risk factors of RAP. Results:The proportion of men, previous biliary disease, hyperlipidemia, diabetes mellitus and previous gallbladder or biliary surgery in recurrent group were significantly higher, while the mean age was significantly lower than that of the initial group. The main causes in the initial group successively were biliary disorders, hyperlipidemia and alcohol, while in the recurrent group were hyperlipidemia, biliary disorders and alcohol. The etiology of hyperlipidemia was significantly higher in the recurrent group than in initial group. The incidence of MAP and regional portal hypertension was significantly higher in the recurrent group, while the incidence of SAP and acute respiratory distress syndrome were significantly lower than those in the initial group, and all the differences were statistically significant(All P value <0.001). The results of the correlation analysis showed that there was no correlation between the severity of RAP and the number of recurrence, and the risk of SAP in RAP did not decrease with the increasing number of recurrence. The results of the multivariate logistic regression analysis showed that previous biliary disorders ( OR=1.303, 95% CI 1.032-1.645, P=0.026), previous history of hyperlipidemia ( OR=2.631, 95% CI 1.580-4.379, P<0.001), and the etiology of hyperlipidemia ( OR=1.773, 95% CI 1.465-2.145, P<0.001) were independent risk factors for RAP. Conclusions:RAP may often occur in middle-aged men and hyperlipidemia is the main cause of RAP, previous history of hyperlipidemia and biliary disease are risk factors for RAP.

The formulation of the best evidence for early fluid resuscitation management of severe acute pancreatitis patients / 中华胰腺病杂志

Objective:To establish the best evidence-based approach for early fluid resuscitation management in patients with severe acute pancreatitis (SAP).Methods:A literature search was conducted utilizing evidence-based nursing methods to identify relevant evidence on the management of early fluid resuscitation in patients with SAP. The search followed the hierarchical order of the " 6S" evidence pyramid, including databases such as China National Knowledge Infrastructure (CNKI), China Biomedical Literature Database (SinoMed), Wanfang Database, UpToDate, NICE, RNAO Guidelines Network, Pancreatology International, WHO Association Website, JBI, Cochrane, PubMed, EMBASE, and CINAHL. The search was limited to articles published from the establishment of each database to March 2022. The literature quality evaluation tools and an evidence pre-grading system from the JBI Evidence-Based Health Care Center were employed to assess the quality of the literature included in the study. Additionally, the FAME structure was utilized to evaluate the feasibility, appropriateness, clinical significance, and validity of the evidence.Results:Nine articles were finally incorporated into the analysis, including four guidelines, one evidence summary, two systematic reviews, and two expert consensus articles. 21 pieces of evidence pertaining to early fluid resuscitation management in patients with SAP was summarized, encompassing five key aspects: resuscitation timing, type of fluid infusion, total volume and speed of fluid infusion, dynamic monitoring, and fluid resuscitation goals. It was advisable for patients diagnosed with SAP to promptly receive fluid resuscitation, ideally within 72 hours of diagnosis. The initial choice for fluid resuscitation was lactated Ringer′s solution, with the addition of human albumin as a supplementary colloid solution. The quantity of fluid administered within the first 24 hours of rehydration should constitute approximately 33.3% of the total rehydration volume within the 72 hours time-frame. In the case of patients experiencing early shock or dehydration, it was advised that the fluid rate administered should be 5-10 ml·kg -1·h -1 within the first 24 hours of admission. Additionally, an infusion of 20 ml/kg of fluid can be administered within the initial 30-45 minutes. It was recommended to assess the adequacy of early fluid resuscitation every 4-6 hours, ensuring that the resuscitation objective could meet at least two of the following criteria: urine output of 0.5-1 ml·kg -1·h -1, mean arterial pressure of 65-85 mmHg, central venous pressure of 8-12 mmHg, heart rate below 120 beats/min, central venous oxygen saturation of at least 70%, and a decrease in hematocrit levels to 30%-35%. Conclusions:The most compelling evidence supporting the implementation of early fluid resuscitation management in patients with SAP is derived from an evidence-based nursing approach, which could effectively improve patient care outcomes.

Predictive analysis of the number of hospitalized patients with acute pancreatitis based on time series model / 中华胰腺病杂志

Objective:To predict and analyze the number of acute pancreatitis (AP) inpatients based on time series model, and to explore the predictive efficiency of the model.Methods:Clinical data of AP inpatients in the Affiliated Hospital of Southwest Medical University from January 2014 to December 2019 were collected. R software was used to collect the time series of AP inpatients, and the trend and seasonal characteristics of AP inpatients from 2014 to 2018 were analyzed. Furthermore, the autoregressive moving average (ARIMA) model was established through stationarity test, model ordering and model testing steps, and the best selected model was used to predict the monthly number of inpatients in 2019 to verify its prediction efficiency.Results:A total of 3 939 AP patients were included in the study. The most common etiology for AP was cholestrogenic (48.2%), followed by hyperacylglyceremia (36.3%). The peak age of hospitalization was from 40 to 60 years old. Time series analysis showed that the number of AP inpatients increased year by year. The highest peak of the disease was from February to March, followed by September to November; and there was seasonal variation and the incidence was relatively small in summer. The established original training set sequence did not pass the stationarity test ( P=0.061), so the ARIMA model was established after it was transformed into a stationarity sequence by first-order difference. According to the criterion of minimum AIC value, ARIMA(2, 1, 1)(1, 1, 1) 12 was selected as the best model. The model was used to predict the number of AP inpatients in 2019, showing that it could better fit the trend of onset time and had good short-term prediction effect. The mean root error and absolute error were 6.8790 and 4.7783, respectively. Conclusions:The number of AP inpatients increases year by year with seasonal changes. ARIMA model is effective in predicting the number of AP inpatients and can be used for short-term prediction.